Background: The objective of this study was to determine the cutoff value of PD-L1 expression that can predict response to immune checkpoint inhibitor (ICI) immunotherapy for upper tract urothelial carcinoma (UTUC).
Methods: The concordance of PD-L1 expression between paired surgical resection specimens (SRSs) and urine cell blocks (UCBs) (cohort 1) was studied in a retrospective set of 58 UTUC patients to determine its suitability as a predictor of ICI immunotherapy efficacy. PD-L1 expression in UCBs obtained before neoadjuvant ICI immunotherapy was verified in a prospective set of 12 UTUC patients (cohort 2). PD-L1 (SP263 clone) expression was assessed for percentage (tumor proportional score) of tumor cell (TC) showing PD-L1 staining.
Results: The authors found an overall agreement of 94.4% (51 of 54) between UCBs and SRSs in cohort 1 (positive percent agreement = 100%, negative percent agreement = 93.8%, r value = 0.63). PD-L1 expression in <10% and ≥10% of tumor cells (TCs) of UCBs were the best predictors of negative (<25%) and positive (≥25%) expression in TCs of SRSs, respectively (concordance = 98.1%, r value = 0.93). These findings were verified in cohort 2: at the 10% cutoff for PD-L1 expression, the best response predictive value was 83.3% (5 of 6) in PD-L1-positive patients, and the nonresponse predictive value was 50% (3 of 6) in PD-L1-negative patients. The sensitivity, specificity, and area under the receiver operating characteristic curve values for predicting ICI immunotherapy efficacy based on PD-L1-expressing TCs in UCBs were 62.5%, 75%, and 0.688, respectively.
Conclusions: Immunocytochemistry of UCBs is reliable for determining PD-L1 expression, which can predict the efficacy of ICI immunotherapy at a cutoff of 10%.
Keywords: PD-L1; UTUC; immunohistochemistry; immunotherapy; urine cell blocks.
© 2022 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.